The principal aims of this project are to delineate hormonal factors that may be involved in the sex-linked protection against atherosclerosis normally exhibited by women. The role of androgens and estrogens as protective or deleterious compounds will be explored by studies of their daily production, biosynthetic precursors, routes and kinetics of metabolism, conjugation mechanisms, plasma concentrations and patterns of secretion in normal control subjects, and patients with atherosclerosis, hypothyroidism, and diabetes. An intensive study will be carried out of precursors, conjugates and metabolites of androsterone, a natural steroid metabolite which is hypolipemic on parenteral administration with the aim of finding an orally-active analog. Studies will be made concerning cholesterol absorption and esterification, the mechanisms causing hypercholesteremia, and the source of cholesterol ester found in the atheroma. When differences may be discerned between normal and atherosclerotic or hyperlipemic subjects thereapeutic trials of the appropriate natural steroids related to androgens and estrogens will be performed in the attempt to find an acceptable compound that would be of benefit in arteriosclerosis, hyperlipemic states, and for the vascular disease of diabetes.